TWI813285B - Integrated nucleic acid processing apparatus - Google Patents

Abstract

The present disclosure provides an integrated nucleic acid processing apparatus including a first operation area, a second operation area and a separation wall. The first operation area includes multiple carrying boards for placing objects and reagents for processing nucleic acids in samples, and multiple functional modules for performing operations of nucleic acid processing. The second operation area includes two extraction regions for respectively performing nucleic acid extractions. The separation wall separates the first operation area from the second operation area and includes two openable door sheets spatially corresponding to the two extraction regions. Nucleic acid extraction plates can be moved from the first operation area to the second operation area by means of the carrying boards as the two openable door sheets are opened, and be isolated in the second operation area for performing nucleic acid extractions as the two openable door sheets are closed.

Description

Integrated nucleic acid processing equipment

This case is about an integrated nucleic acid processing equipment, especially a highly automated integrated nucleic acid processing equipment.

Currently, nucleic acids in biological samples need to go through multiple processing procedures before detection and analysis, such as reading the barcode of the collection tube, opening and closing the lid, sample transfer, nucleic acid extraction, preparation of detection reagents, etc., which involves many operating steps, and this Most of these operation steps still need to be performed manually. This not only affects the detection efficiency and accuracy, but also increases the risk of cross-contamination between samples and operator infection.

In order to improve detection efficiency, especially in response to the rapid and large-scale detection needs when major public health diseases occur, many automated equipment have been developed to assist operators. However, most of these detection equipment can only integrate a part of the processing procedures to perform automated operations. , especially nucleic acid extraction operations. When using magnetic bead nucleic acid extraction operations, it is easier to generate aerosols and cause cross-contamination. Therefore, they are often performed separately, so the manual operation burden cannot be effectively reduced. Moreover, these detection equipment are generally bulky and expensive. It is expensive and not suitable for small and medium-sized hospitals.

Therefore, it is necessary to develop an integrated nucleic acid processing equipment that can effectively reduce the size of the equipment and integrate multiple processing procedures to perform automated operations to reduce the burden of manual operations.

The purpose of this case is to provide an integrated nucleic acid processing equipment, which integrates the nucleic acid processing procedures before nucleic acid detection, so as to achieve the purpose of fully automated operation.

Another purpose of this case is to provide an integrated nucleic acid processing equipment that minimizes volume through internal space configuration.

Another purpose of this case is to provide an integrated nucleic acid processing equipment that utilizes space allocation and partitioning to effectively reduce the probability of cross-contamination during nucleic acid extraction operations, so that nucleic acid extraction operations can also be integrated into the same equipment and executed automatically.

In order to achieve the above purpose, this case provides an integrated nucleic acid processing equipment, including a first operating area, a second operating area, and a partition wall. The first operating area includes a collection tube carrier plate, a pipette carrier plate, two extraction reagent well plate carrier plates, a barcode scanner, a pipette gun module, a switch cover module, and a visual identification module. group. The collection tube carrier plate is used to place a plurality of collection tubes, and the pipette carrier plate is used to place at least one pipette rack, and each pipette rack includes a plurality of pipettes, and each extraction reagent well plate The carrier plate carries a plurality of extraction reagent well plates, and each extraction reagent well plate is preset with a plurality of magnetic rod sets. The barcode scanner is used to scan a plurality of barcodes set on a plurality of collection tubes. The pipette gun model The set is used to combine a plurality of pipettes to move a plurality of samples from a plurality of sampling tubes to at least one of a plurality of extraction reagent well plates, and the switch cover module is used to open and close the plurality of sampling tubes. The plurality of covers and the visual recognition module include a camera for capturing internal images of the first operating area. Among them, the collection tube carrying plate, the pipette carrying plate, and the two extraction reagent well plate carrying plates are respectively set up on a track to move in the X-axis direction, and the pipette gun module and the visual recognition module are mounted on the Y axis direction and Z-axis direction. The second operating area is divided into two extraction areas up and down, and each extraction area includes a magnetic rod rack for setting up a plurality of magnetic rods, and a magnetic rod sleeve connector rack for setting up a plurality of magnetic rod sleeve connectors. , to connect the isomagnetic rod set pre-placed in the isoextraction reagent well plate. The partition wall is used to separate the first operating area and the second operating area, and includes two door pieces, corresponding to the two extraction areas respectively. The two extraction reagent well plate carrier plates are arranged up and down corresponding to the two door pieces, and can be moved from the first operating area to the second operating area when the two door pieces are opened, and can be executed in the isolated second operating area when the two door pieces are closed. A plurality of nucleic acid extraction operations using a plurality of magnetic rods, a plurality of magnetic rod sleeve connectors, and a plurality of magnetic rod sleeves.

In one embodiment, the two extraction reagent well disk carrier plates are arranged up and down, and the extraction reagent well disk carrier plate and the sampling tube carrier plate located below are located on a first plane, and the two can be selectively coupled mechanically And move synchronously.

In one embodiment, the pipette carrier plate is located on a second plane, and the second plane is higher than the first plane, and the extraction reagent well plate carrier plate located below is located on a third plane, and the third plane is higher on the second plane.

In one embodiment, a housing is further included so that an independent space is formed inside the integrated nucleic acid processing equipment, and the housing has a door for opening.

In one embodiment, the door, the first operating area, and the second operating area are arranged sequentially along the X-axis direction.

In one embodiment, the first operating area and the second operating area each have an independent air circulation system, and each air circulation system has an air flow direction from a lower place to a higher place.

In one embodiment, a high-efficiency filter (HEPA) is further included to filter air entering and exiting the first operating area and the second operating area respectively.

In one embodiment, the collection tube carrying plate has a plurality of hollow portions corresponding to a plurality of collection tubes, and the barcode scanner includes a bottom scanner to scan a plurality of barcodes provided at the bottom of the plurality of collection tubes.

In one embodiment, the barcode scanner includes a side scanner to scan a plurality of barcodes provided on the sides of a plurality of collection tubes.

In one embodiment, the sampling tube carrying plate has a first sampling tube placement area and a second sampling tube placement area to respectively carry different types of sampling tubes.

In one embodiment, a nucleic acid detection tray is further placed on the collection tube carrier plate to accommodate nucleic acids obtained after a plurality of nucleic acid extraction operations.

In one embodiment, a reagent tube rack is further placed on the sampling tube carrying plate to place a plurality of reagent tubes, and a cooling module is arranged corresponding to the reagent tube rack.

In one embodiment, the plurality of pipettes are placed back into at least one pipette rack after use.

In one embodiment, a well plate is further placed on the pipette carrier plate to serve as a nucleic acid detection plate or an extraction nucleic acid sample retention plate.

In one embodiment, each extraction reagent well plate carrier plate includes a heating module to provide temperature changes required for a plurality of nucleic acid extraction operations.

In one embodiment, the switch cover module includes a screw switch cover module and a claw switch cover module.

In one embodiment, it further includes a plurality of chassis, which are respectively disposed under the pipetting gun module and the switch cover module.

In one embodiment, it further includes ultraviolet (UV) lamps, which are respectively installed in the first operating area and the second operating area for cleaning and sterilization.

In one embodiment, it further includes a controller and at least one motor to respectively control and drive the collection tube carrier plate, the pipette carrier plate, the two extraction reagent well plate carrier plates, the pipette module, and the barcode scanner. , visual identification module, magnetic rod holder, magnetic rod sleeve connector holder, and two door pieces.

Some typical embodiments embodying the features and advantages of this case will be described in detail in the following description. It should be understood that the present invention can have various changes in different aspects, but all do not depart from the scope of the present invention, and the description and illustrations are for illustrative purposes in nature, not for limitation. invention.

Please refer to Figure 1, which shows a schematic diagram of the integrated nucleic acid processing equipment according to the embodiment of the present case. As shown in the figure, the integrated nucleic acid processing equipment 1 in this case has a shell 10 to form an internal space that is independent and isolated from the external environment, and a door 11 that can be temporarily opened for related operations in and out of the internal space, such as placing or moving parts. Except etc. In addition, the integrated nucleic acid processing equipment 1 also includes a controller (not shown) to control various nucleic acid processing procedures performed in the internal space, and the housing 10 is also provided with an operation interface 12, such as a touch screen, which is electronic. Connected to the controller for operators to control the integrated nucleic acid processing equipment 1.

Please refer to Figures 2A and 2B. Figure 2A shows a schematic diagram of the door 11 and its installation components according to the embodiment of the present case. It is a view from the inside to the outside of the integrated nucleic acid processing equipment 1, and Figure 2B shows the diagram in Figure 2A. An enlarged view of circle A. The door 11 has a door frame 111, a door panel 112 and a handle 113, and the door 11 is installed on a driving side slide rail 102 and a driven side slide rail 103 through a pair of linear modules 101, so that it can perform up and down operations. Switching operation, that is, switching operation along the Z-axis direction. The driving side slide rail 102 and the driven side slide rail 103 are installed inside the integrated nucleic acid processing equipment 1 through a plurality of mounting brackets 104 . In one embodiment, the door panel 112 may be made of acrylic.

The linear module 101 includes a door bracket 1011, a cam 1012, a spring 1013, a spring bracket 1014, a linear guide rail 1015, a sliding plate 1016 and a slider 1017. The slider 1017 is combined with the driving side slide rail 102 and the driven side slide rail 103 respectively. The slider 1016 is set on the slider 1017. The linear guide rail 1015 is set on the slider 1016. The door bracket 1011 is set on the linear guide rail 1015 and is connected with the door at the same time. The door frame 111 of 11 is locked and combined, so when the slider 1017 slides along the driving side slide rail 102 and the driven side slide rail 103, it can drive the door 11 to slide up and down. In addition, the spring bracket 1014 is set on the sliding plate 1016, one end of the spring 1013 is set on the spring bracket 1014, and the other end is set on the door bracket 1011, and the setting direction of the spring 1013 is parallel to the linear guide rail 1015, and the setting direction of the linear guide rail 1015 The direction is perpendicular to the driving side slide rail 102 and the driven side slide rail 103. In other words, the linear guide rail 1015 is used for the door bracket 1011 to move back and forth in a direction perpendicular to the door up and down opening and closing operations, that is, to move along the X-axis direction. Accordingly, when the door bracket 1011 disposed on the slide plate 1016 through the linear guide rail 1015 moves along the linear guide rail 1015 on the slide plate 1016, the spring 1013 can provide tensile elastic force along the direction of the linear guide rail 1015. Here, movement toward the outside of the device is defined as forward movement, and movement toward the inside of the device is defined as backward movement.

The driving side slide rail 102 and the driven side slide rail 103 are further provided with a guide plate 105 respectively, which is installed at the door closing height, and each guide plate 105 has a groove 1051. In addition, the door bracket 1011 is further provided with a cam 1012. , and when the door 11 is pulled down to close, the cam 1012 can slide into the groove 1051. Since the groove 1051 has a slope, it gradually moves away from the inside of the integrated nucleic acid processing equipment 1 from top to bottom, that is, it slopes downward and toward the outside of the equipment. Therefore, during the closing process, when the cam 1012 slides into the groove 1051 , will drive the door bracket 1011 to move toward the outside of the equipment on the linear guide rail 1015, so that the door 11 moves forward while descending as it closes downward, and then gradually presses against the shell 10 in contact with the door 11, and completes the closing of the door. operate. At this time, the spring 1013 is in a stretched state, but since the cam 1012 is stuck in the groove 1051, the pulling force of the spring 1013 will not affect the position of the door 11.

When the door opening operation is performed, the slider 1017 on the linear module 101 drives the sliding plate 1016 to move upward, and the door 11 also moves upward. At this time, the cam 1012 slides along the groove 1051, and drives the door bracket due to the slope of the groove 1051. 1011 slides on the linear guide 1015 in the direction toward the inside of the integrated nucleic acid processing equipment 1. At the same time, the tension of the spring 1013 also acts. Therefore, the door 11 moves backward while rising while opening the door. When the door 11 rises to a certain height, the cam 1012 breaks away from the groove 1051 to fix the door 11 in the rear position, so that it does not touch other structures during the rising process, and the closing operation is completed after rising to the final height.

Next, please refer to Figures 3A-3B. Figure 3A shows a perspective view of the integrated nucleic acid processing equipment 1 of this embodiment, and Figure 3B shows a perspective view of the integrated nucleic acid processing equipment 1 of this embodiment from another angle. The integrated nucleic acid processing equipment 1 includes a first operating area 20, a second operating area 30, and an electromechanical configuration area 40. The first operating area 20 and the second operating area 30 are the main spaces for performing nucleic acid processing. The electromechanical configuration area 40 is equipped with various electromechanical components required for the operation of the integrated nucleic acid processing equipment 1, such as motors, motor controllers, and power boxes. , integrated circuit boards, industrial computers and other related components required for electronic control. The spatial relationship of each operating area in the integrated nucleic acid processing equipment 1 is that the door 11, the first operating area 20 and the second operating area 30 are arranged sequentially along the X-axis direction, that is, the first operating area 20 is longer than the second operating area. The operating area 30 is closer to the door 11 , and in addition, the electromechanical configuration area 40 is located above the second operating area 30 .

The first operating area 20 and the second operating area 30 are separated by a partition wall 50 , so that the first operating area 20 and the second operating area 30 are separate and independent spaces. That is, they are separated in the first operating area 20 and the second operating area 30 . The nucleic acid processing procedures carried out in the operation area 20 and the second operation area 30 are separated from each other by the partition wall 50 , thus effectively avoiding cross-contamination that may be caused by air circulation between the two operation areas, such as nucleic acid samples flying along with aerosols. cross-contamination.

The first operating area 20 and the second operating area 30 are respectively used to perform different nucleic acid processing procedures. In the first operating area 20, processing procedures such as sampling tube barcode reading, sample transfer, and analysis reagent configuration are performed, and the second operating area 20 is used to perform different nucleic acid processing procedures. The nucleic acid extraction process, such as the magnetic bead method nucleic acid extraction process, is performed in the operation area 30 . In other words, in the pretreatment process of nucleic acid analysis, except for the nucleic acid extraction process, other processes are performed in the first operation area 20 . The consideration for this allocation is that the magnetic bead nucleic acid extraction process involves vigorous shaking of the extraction reagent liquid and the movement of the magnetic rod sleeve, which is more likely to generate aerosols and cause cross-contamination. Therefore, the nucleic acid extraction process is separated into a separate second operation. The area 30 is beneficial to maintaining the cleanliness of the internal space of the integrated nucleic acid processing equipment 1 .

Under the above premise, the first operating area 20 and the second operating area 30 are respectively provided with independent air circulation systems, including a first air inlet 21a and a first air outlet 21b provided in the first operating area 20, and There is a second air inlet 31a and a second air outlet 31b in the second operating area 30, and as shown in the figure, the first air inlet 21a and the second air inlet 31a are located lower than the first air outlet 21b and the second air outlet 31b. The installation position of the second air outlet 31b. The advantage of this configuration is that the air entering each operating area will have a flow direction from low to high, that is, the air will gradually rise without a tendency to sink. Therefore, even if there is air in the air, Sols and aerosols will also move toward the outlet along with the gradually rising air flow direction, and will not increase the chance of contaminating the sample due to sinking. In one embodiment, high-efficiency filters (HEPA) can be used to dispose the air inlets 21a and 31a and the air outlets 21b and 31b to ensure that both the air entering and exiting the integrated nucleic acid processing equipment 1 is clean air. In addition, based on different needs, the execution parameters of the air circulation system in the first operating area 20 and the second operating area 30 , such as air flow speed and air volume, can be set differently. For example, since the second operating area 30 is used to perform nucleic acid extraction procedures that are more likely to produce aerosol pollution, the air circulation system of the second operating area 30 can be set to have a larger air flow rate, flow rate, etc. So that the generated aerosols can be eliminated faster. In addition, the first operating area 20 and the second operating area 30 may also be respectively provided with ultraviolet (UV) lamps to illuminate the interior of each operating area to achieve a cleaning and sterilizing effect.

The first operating area 20 is provided with an operating function module set 26, which is hung above the internal space to complete the execution of the above-mentioned various programs. In addition, below the operating function module set 26, there is an operating function module set 26 for placing everything during the operation. A collection of load-bearing plates for various components is required.

Please refer to FIG. 4 , which shows a schematic diagram of the load-bearing plate assembly in the first operating area 20 in this embodiment. In order to achieve the purpose of automated operation, the first operating area 20 is designed to have multiple carrying plates to carry parts classified according to operating procedures, including a collection tube carrying plate 22 and a pipette carrying plate 23 , and two extraction reagent well plate carrier plates 24a and 24b. In addition, the first operating area 20 also includes a plurality of baffles 27 (shown in Figure 3A and Figure 3B), which are arranged around the first operating area 20 to block the mechanical structure and leave space for the movement of the load-bearing plate. This system can flatten the space in the operating area and reduce dead corners in internal gaps, thereby preventing samples from accidentally remaining in the gaps and increasing the chance of cross-contamination, and making it easier to clean and wipe the interior of the operating area.

Please continue to refer to Figure 4 and Figures 5A-5B, 6, and 7A-7B. Figure 5A shows a schematic diagram of the inspection tube carrier plate 22 and its configuration in the embodiment of this case. Figure 5B shows the inspection of the embodiment of this case. Another schematic view of the pipe support plate 22 and the configuration thereon. Figure 6 shows a schematic view of the pipette support plate 23 and the configuration thereon in this embodiment. Figure 7A shows the extraction reagent well plate support plate 24a in this embodiment. A schematic diagram of the extraction reagent well plate carrier plate 24b and its configuration in the embodiment of this case is shown in Figure 7B. As shown in Figure 4, the sampling tube carrier plate 22, the pipette carrier plate 23 and the two extraction reagent well plate carrier plates 24a and 24b are respectively installed on corresponding tracks and driven by a motor (not shown) And moving along the X-axis direction on the track, that is, moving in the direction perpendicular to the door 11. In other words, by moving along the X-axis direction of the track, each bearing plate can move to a position close to the door 11 to facilitate the operator. The corresponding parts are placed on each carrying plate, and after the placement is completed, they are moved away from the door 11 along the track and toward the inside of the first operating area 20 .

There is a specific spatial configuration relationship between each load-bearing plate. The sampling tube bearing plate 22 and the extraction reagent well plate bearing plate 24b are located on the same first plane, and the sampling tube bearing plate 22 is disposed between the extraction reagent well plate bearing plate 24b and the door 11, that is, the sampling tube The tube carrier plate 22 is closer to the door 11 than the extraction reagent well plate carrier plate 24b, the pipette carrier plate 23 is located on a second plane, and the second plane is higher than the first plane, and the extraction reagent well plate carrier plate 24a is located on a first Three planes, and the third plane is higher than the second plane. In other words, the plurality of bearing plates form three moving planes in the first operating area 20 . Through the design of different plane heights, the pipette carrying plate 23 and the extraction reagent well plate carrying plate 24a can be moved to a position close to the door 11 to facilitate the operator to place parts. In addition, since when the extraction reagent well plate carrying plate 24a moves toward the door 11, it will pass above the pipette carrying plate 23, so in order to avoid collision with the parts carried on the pipette carrying plate 23, the extraction reagent well plate carrying plate 24a The plate 24a is further provided with a sensor (not shown) to sense whether there are parts placed on the pipette carrying plate 23. In addition, the sampling tube carrier plate 22 and the extraction reagent well plate carrier plate 24b located on the same plane can be further mechanically combined, for example, through magnetic coupling to move synchronously, so that they only need to be driven by a single motor to move, which is more convenient. . In addition, when the extraction reagent well plate carrier plate 24b does not need to be moved, it can also be pushed into the second operating area 30, thereby releasing the space originally occupied by the sampling tube carrier plate 22 for movement.

The sampling tube carrying plate 22 is mainly used to place the sampling tube 220 . In response to the different forms of currently used inspection tube racks, the inspection tube carrying plate 22 is divided into a first inspection tube placement area 221 and a second inspection tube placement area 222, where the first inspection tube placement area 221 It is used to place the row-type sampling tube rack 2201, and the second sampling tube placement area 222 is used to place the disk-type sampling tube rack 2202. With this design, when there are different forms of sampling tubes, you only need to selectively place them in the corresponding placement area according to the form of the sampling tubes, so that the purpose of universally accepting various forms of currently used sampling tubes can be achieved. In one embodiment, the first sampling tube placement area 221 can place 8 row-type sampling tube racks 2201, and each row-type sampling tube rack 2201 can place 8 sampling tubes 220; in another implementation In this example, the second sampling tube placement area 222 can place a 4 x 8 disk type sampling tube rack 2202, but is not limited to this. In addition, sampling tubes with different diameters can also be placed through row-type sampling tube racks 2201 or disc-type sampling tube racks 2202 of different sizes, so the applicability of the equipment can be improved.

Furthermore, a barcode scanner is provided in the first operating area 20 to scan the barcode on the sampling tube 220 placed on the sampling tube carrier plate 22 . Since the sampling tube carrying plate 22 will be moved to a position close to the door 11 when the sampling tube 220 is placed, the barcode scanner is preferably disposed close to the door 11 . The first collection tube placement area 221 and the second collection tube placement area 222 are both equipped with sensors (not shown) to sense whether a collection tube rack is placed and to identify where the collection tube rack is placed. Position, the controller can drive the barcode scanner to perform the scanning action accordingly.

In one embodiment, a bottom scanner 25a can be provided to scan the barcode provided at the bottom of the collection tube 220, and correspondingly, the first collection tube placement area 221 and the second collection tube placement area 222 are both provided with The plurality of hollow portions 223 are used to expose the barcodes provided at the bottoms of the plurality of sampling tubes 220; the side walls surrounding each of the hollow portions 223 help to separate adjacent barcodes and avoid reading errors. In another embodiment, a side scanner (not shown) can also be provided to scan the barcode provided on the side of the collection tube 220. Here, the side scanner is mainly used for row-type collection tubes. The sampling tube 220 on the rack 2201 (that is, the sampling tube 220 placed at the first sampling tube placement area 221) is scanned with a barcode, so the sensor installed at the first sampling tube placement area 221 will The position of the currently inserted row-type sampling tube rack 2201 is further sensed as a basis for the side scanner to adjust the scanning focus. That is, the side scanner will adjust the position of the row-type sampling tube rack 2201 according to the distance between it and the row-type sampling tube rack 2201. Adjust the focus to get clear barcodes.

In addition, the collection tube carrying plate 22 can also carry a nucleic acid detection tray 224 or a plurality of detection row tubes (not shown) to accommodate the nucleic acid obtained after the nucleic acid extraction operation. In one embodiment, the nucleic acid detection tray 224 is It has 96 receiving holes, or can be replaced with 12 8-hole detection tubes. In addition, the sampling tube carrying plate 22 can also carry a reagent tube rack 225 to place a plurality of reagent tubes 2250 for accommodating analysis reagents, for example, 24 reagent tubes, and further, a reagent tube rack 225 can be placed between the corresponding reagent tube racks 225. A cold storage module 226 is provided at the placement location, such as a cooler, to maintain the reagent at a low temperature, thereby maintaining the quality and performance of the reagent.

The sampling tube carrying plate 22 is further provided with a replaceable rotating plate 227, which can be replaced according to needs to choose to set a nucleic acid detection tray, a plurality of detection tubes and/or reagent tube racks, or to place a row of detection tubes Rack or disk-type sampling tubes increase the flexibility of use.

The pipette carrying plate 23 is mainly used to carry a plurality of pipettes 230 for transferring liquids in nucleic acid processing procedures, and the plurality of pipettes 230 are arranged in a pipette rack. In one embodiment, two 96-well pipette racks 2301a and one 24-well pipette rack 2301b can be provided on the pipette carrier plate 23 to accommodate pipettes 230 of various volumes, for example, 1000 μL, 200 μL, 50 μL and/or 10 μL pipettes. There is a pipette 230 corresponding to each placement hole, that is, each pipette 230 has a separate placement space. Therefore, the pipette 230 can be put back into the original placement hole again after use, and it will not Contamination of unused adjacent pipettes occurs, and it can also avoid the problem in the prior art that when pipettes are discarded in another container, the stacking space may be higher than the height of the container due to different discard angles, thereby affecting the movement of the carrier plate. condition. Here, the type and quantity of the pipette rack and the type and quantity of pipettes it can accommodate can be changed according to actual needs, and are not limited to those shown in the figure. In addition, the pipette carrier plate 23 can also be placed with a well plate 231, such as a 96-well plate, which can be selectively used for a variety of purposes, such as a nucleic acid detection plate, or a nucleic acid extraction sample retention plate, etc., to increase operational flexibility. .

The extraction reagent well disk carrier plates 24a and 24b are both used to carry the extraction reagent well disk 241. For example, each extraction reagent well disk carrier plate can carry three extraction reagent well disks for nucleic acid extraction operations. Each extraction reagent well disk is used for nucleic acid extraction operations. Reagents required for the nucleic acid extraction process and magnetic rod sets (not shown) are preset in the reagent well plate 241 . In addition, the extraction reagent well plate carrier plates 24a and 24b are provided with a heating module 242, such as a heater, corresponding to the position where the extraction reagent well plate 241 is placed, to provide temperature changes required for the nucleic acid extraction process, such as changing the temperature according to the operating procedure. And adjust to 60℃ or 80℃. It should be noted that the extraction reagent well plate carrier plates 24a and 24b are provided with heating modules 242 at positions corresponding to each extraction reagent well plate 241. Figures 7A and 7B are only perspective illustrations corresponding thereto for simplicity. A heating module 242 for extracting the reagent well plate 241. Furthermore, as shown in Figure 4, the extraction reagent well plate bearing plates 24a and 24b have an up-down spatial relationship, that is, the third plane where the extraction reagent well plate bearing plate 24a is located is higher than the extraction reagent well plate bearing plate. The first plane where 24b is located.

Please continue to refer to Figure 8, which shows a perspective view of the second operating area 30 of this embodiment. The second operation area 30 is divided into two extraction areas 31 and 32, upper and lower, and the partition wall 50 that separates the first operation area 20 and the second operation area 30 is provided with two doors corresponding to the two extraction areas 31 and 32. 51a, 51b, and the positions of these two door pieces 51a, 51b further correspond to the height positions of the extraction reagent well plate carrier plates 24a, 24b, so as to allow the extraction reagent well plate carrier plates 24a, 24b and the extraction reagent well plate 241 thereon to pass through. That is, the extraction reagent well disk carrier plates 24a and 24b and the extraction reagent well disk 241 thereon can be moved from the first operating area 20 into the second operating area 30 through the spaces exposed by opening the door pieces 51a and 51b respectively. In addition, the two extraction areas 31 and 32 are respectively provided with slide rails 313 and 323 for respectively allowing the extraction reagent well plate carrier plates 24a and 24b to slide into the second operation area 30 .

As mentioned above, the second operation area 30 is used to perform nucleic acid extraction operations. Therefore, the extraction reagent well plate 241 loaded in the first operation area 20 needs to enter the second operation area 30. Therefore, in this case, in the first operation On the premise that the area 20 and the second operation area 30 are separated by the partition wall 50, openable door pieces 51a and 51b are provided to allow the extraction reagent well plate carrier plates 24a and 24b to temporarily pass through, and the nucleic acid extraction is performed. Closing during operation to provide an isolated operating space can achieve automated operations while minimizing the chance of cross-contamination between samples. Here, it is preferable that the door pieces 51a and 51b open and close in a straight up and down manner to save space for opening and closing the door; it is even more preferable that the door pieces 51a and 51b can be opened and closed automatically to make the operation process smoother. In one embodiment, the automatic opening and closing of the door blades 51a and 51b can be achieved by arranging a motor, a linear motion slide rail, a synchronous pulley, a synchronous belt, etc.

The second operation area 30 is equipped with a mechanism for performing the magnetic bead nucleic acid extraction operation, and the two extraction areas 31 and 32 have the same configuration and can respectively perform the same magnetic bead nucleic acid extraction operation to increase the number of processes that can be processed simultaneously. Number of samples. The extraction areas 31 and 32 respectively include magnetic rod racks 311 and 321 for erecting a plurality of magnetic rods 3111 and 3211, and magnetic rod sleeve connector racks 312 and 322 for erecting a plurality of magnetic rod sleeve connectors 3121 and 3221. , wherein the magnetic rod sleeve connectors 3121 and 3221 are used to connect the magnetic rod sleeves pre-placed in the extraction reagent well plate 241. It should be noted that Figure 8 only illustrates a row of 8 magnetic rods 3111, 3211 and a row of 8 magnetic rod sleeve connectors 3121, 3221 in each extraction zone for simplicity. The magnetic rods and The number of magnetic rod sleeve connectors is not limited. In one embodiment, three extraction reagent well disks 241 are respectively carried on the corresponding extraction reagent well disk carrier plates 24a and 24b, and each extraction reagent well disk 241 can process two groups of 8 samples. Therefore, each extraction reagent well disk 241 can process two groups of eight samples. One magnetic rod rack 311, 321 can be correspondingly provided with 6 rows of a total of 48 magnetic rods 3111, 3211, and each magnetic rod sleeve connector rack 312, 322 can also be correspondingly provided with a total of 6 rows of 48 magnetic rod sleeve connectors 3121, 3211. 3221.

Since the operation processes in the two extraction zones 31 and 32 are the same, the following description will only take the extraction zone 31 as an example. The actual operation can be performed in either extraction zone alone or in the two extraction zones at the same time according to the needs, without limitation. . The nucleic acid extraction operation process is as follows: the door piece 51a is opened, and after the extraction reagent well disk bearing plate 24a enters the extraction area 31, the door piece 51a is closed, and then the magnetic rod sleeve connector frame 312 moves downward to allow the magnetic rod sleeve connector 3121 is combined with the magnetic rod sleeve in the extraction reagent well plate 241, and then, by moving the magnetic rod sleeve connector 312 up and down, the magnetic rod sleeve combined with the magnetic rod sleeve connector 3121 can be placed in each of the extraction reagent well disk. The steps of magnetic bead nucleic acid extraction, such as cell lysis, nucleic acid adsorption, cleaning, and elution, are performed sequentially in the wells. During this process, when it is necessary to absorb magnetic beads, the magnetic rod holder 311 moves downward so that the magnetic rod 3111 disposed thereon passes through the magnetic rod sleeve connector 3121 and extends into the bottom of the magnetic rod sleeve to absorb the magnetic beads. The magnetic beads in the wells of the reagent well plate 241 are extracted, and then the magnetic rod holder 311 and the magnetic rod sleeve connector holder 312 move together to move the magnetic beads to the next well. After that, the magnetic rod holder 311 moves upward again to separate the magnetic rod 3111 and the magnetic beads, thereby releasing the magnetic beads. At the same time, the magnetic rod sleeve can be driven by the magnetic rod sleeve connector frame 312 to vibrate up and down to actively accelerate. The magnetic beads spread out and mix with the liquid.

Since the magnetic bead nucleic acid extraction operation requires the magnetic rod sleeve to move up and down in the wells of the extraction reagent well plate 241 and between the wells sequentially, that is, to move along the Z-axis and Y-axis directions, it is necessary to ensure that the magnetic rod sleeve There will be no deviation in the movement of the magnetic rod, that is, it can maintain linear movement. Therefore, the magnetic rod frame 311 and the magnetic rod sleeve connector frame 312 are further provided with linear lead screw groups (not shown), so that whether they move up and down or left and right, they can move accurately without deviation; in addition, because the magnetic rod The frame 311 and the magnetic rod sleeve connector frame 312 also need to move together, so linear slide rails and roller clamping can be used to ensure that they do not misalign when they move at the same time.

Next, please refer to Figures 9A-9B and Figure 10. Figure 9A shows a perspective view of the operating function module set 26 of the embodiment of the present invention, and Figure 9B shows another angle of the operating function module set 26 of the embodiment of the present case. Perspective views, and the angles of view in Figures 9A and 9B correspond to the angles of Figures 3A and 3B respectively, and Figure 10 shows an exploded schematic diagram of the operating function module set 26 of the embodiment of the present invention. The movement direction of the operation function module set 26 is perpendicular to the movement direction of the bearing plate, that is, it moves along the Y-axis direction. In other words, each bearing plate 22, 23, 24a, 24b is in the lower space of the first operating area 20 Moving along the X-axis, the operating function module assembly 26 moves along the Y-axis in the upper space of the first operating area 20 .

The operating function module set 26 includes a base 260, a pipetting gun module 261, a screw switch cover module 262, a gripper switch cover module 263, and a visual recognition module 264. The base 260 is combined with each module to provide each module with the power to move independently along the Z-axis and perform its own operations; in other words, each module can move in the Y-axis direction and the Z-axis direction. In addition, each module is coupled to the base 260 through an independent fixing plate, so it can be independently disassembled to facilitate subsequent maintenance.

The pipette module 261 is used to be combined with the pipette 230 (as shown in Figure 6) to perform liquid movement and mixing, for example, moving the liquid in the sampling tube 220 to the extraction reagent well plate 241 , or move the extracted nucleic acid to the nucleic acid detection plate 224 or the well plate 231 . The pipette module 261 includes at least one pipette assembly 2611, a pipette fixing plate 2613 for fixing to the base 260, and at least one chassis 2614 that can receive possible drops from the pipette 230 during movement. The pipette gun group 2611 includes a pipette gun 2612 to automatically grab the pipette 230 and automatically remove the pipette 230 after use. In one embodiment, the pipette gun module 261 is composed of four pipette gun groups 2611, and each pipette gun group 2611 can move along the Z-axis independently.

The screw cover switch module 262 and the claw switch cover module 263 are used to perform the cover opening and closing operation of the sampling tube. The advantage of having both cover switch modules at the same time is that it can universally accept different types of sampling tubes. The screw cover module 262 performs the cover opening and closing procedure for the sampling tube sealed with a cover with threads on both sides. In one embodiment, the screw switch cover module 262 includes a plurality of cylindrical bodies 2621, each cylindrical body 2621 is provided with a thread 2622 at the front end, and each cylindrical body 2621 can move along the Z-axis independently, and uses the thread 2622 It is combined with the thread on one side of the lid of the sampling tube in a tightening manner, that is, the lid on this side is also provided with a corresponding thread 2622 structure to achieve tightening and unscrewing between the two. In addition, the screw switch cover module 262 also includes at least one chassis 2624 to receive liquid that may drip from the cover of the sampling tube 220 .

During the cover opening and closing operation, the arrangement closeness of the plurality of columnar bodies 2621 corresponds to the arrangement closeness of the sampling tubes 220, so the opening and closing cover operations of the plurality of sampling tubes can be performed at the same time, and through such a form of screw opening and closing the cover mold Group 262 can complete the cover opening and closing procedure without occupying additional space. That is, the space above the sampling tube itself is enough to complete the cover opening and closing procedure. Therefore, the sampling tubes 220 can be arranged closely to maximize the amount of food that can be received at a time. quantity, helping to speed up sample processing.

The gripper opening and closing cover module 263 performs a cover opening and closing procedure for the sampling tube sealed with a cover with threads on one side. The clamping jaw switch cover module 263 includes a clamping jaw 2631 that can move along the Z-axis to perform the cover opening and closing action by clamping and grabbing the cover, and the clamping jaw 2631 can rotate 360 degrees to adjust the clamp according to different types of covers. Tight and grasping angle.

The visual recognition module 264 is used to capture images inside the first operating area 20 to identify various components in the space and the information on them, such as identifying shapes, identifying colors, and identifying one-dimensional/two-dimensional barcodes on the components. , identify whether the setting position of the parts is correct, etc., to ensure that the movement of each module in the operating function module set 26 and the placement of the parts placed on each bearing plate are correct, and the operation process proceeds smoothly. In one embodiment, the visual recognition module 264 includes a camera and a light source to obtain a clear image, and obtains required information from the image through algorithm operation. In addition, the visual recognition module 264 also includes a bracket 2641 to be coupled to the base 260 .

Under the aforementioned structure, the overall operation process is: the door 11 is opened; the extraction reagent well plate carrier plate 24a is moved to a position close to the door 11 and the extraction reagent well plate 241 is placed on it, and then moves away from the door 11 and enters the second step. Extraction area 31 of the second operating area 30; the pipette carrier plate 23 is then moved to a position close to the door 11 and placed with the pipette racks 2301a, 2301b and the well plate 231, and then moves away from the door 11 to close to the partition wall 50; the sampling tube carrying plate 22 and the extraction reagent well plate carrying plate 24b are moved to a position close to the door 11, the extraction reagent well plate group 241 is placed on the extraction reagent well plate carrying plate 24b, and the extraction reagent well plate group 241 is placed on the collecting tube carrying plate 22 Place the row-type sampling tube rack 2201 and/or the disk-type sampling tube rack 2202, the reagent tube rack 225 and the nucleic acid testing tray 224. At this time, if the row-type sampling tube rack 2201 is placed, the side scanner will Barcode scanning is performed at the same time; after placement is completed, door 11 is closed.

Next, the visual recognition module 264 captures the internal image of the first operating area 20 to confirm the location, quantity, barcode, etc. of all parts. At this time, if there is a disk-type inspection tube rack 2202, the bottom scanner 25a will perform barcode scanning. , In addition, the pipette module 261 can confirm whether the amount of the detection reagent is sufficient by detecting the liquid level position of the reagent and combining it with the liquid volume estimation calculation. If the amount of the reagent is found to be insufficient, a warning is issued to notify the operator to replenish the reagent.

Once everything is confirmed, the operation will begin. In the first operation area 20, a process of transferring the liquid in the sampling tube 220 placed on the sampling tube carrier plate 22 to the extraction reagent well plate 241 placed on the extraction reagent well plate carrier plate 24a and/or 24b is performed. After the transfer is completed, the extraction reagent well plate 241 enters the extraction area 31 and/or 32 of the second operation area 30 along with the extraction reagent well disc carrier plate 24a and/or 24b to perform the nucleic acid extraction operation; at the same time, the third The configuration of detection reagents can be performed in an operation area 20; then, the extracted nucleic acids in the extraction reagent well plate 241 are further transferred to the nucleic acid detection plate 224 placed on the sampling tube carrier plate 22. At this point, the automatic operation procedure is completed, the door 11 is opened, and the operator takes out the nucleic acid detection disk 224 for subsequent nucleic acid analysis.

Here, from the time when the door 11 is closed and the automatic operation is started until the door 11 is opened, the air circulation system in the first operating area 20 and the second operating area 30 is continuously opened to maintain a single direction of airflow from a lower place to a higher place. After the operation is completed, after the operator has taken out other components on the load-bearing board and emptied the inside of the equipment, the door 11 is closed again, and the UV lamp and air circulation system are turned on to clean the interior for the next use.

To sum up, the integrated nucleic acid processing equipment 1 of the present invention uses partition walls 50 so that the first operating area 20 and the second operating area 30 can be separated from each other, and processing procedures can be executed at the same time without affecting each other. In addition, through the functionally classified bearing plate design, each bearing plate can move independently along the X-axis, and with the operation of the functional module set 26, it can move along the Y-axis, and each internal module can also independently move along the Z-axis at the same time. Movement can effectively reduce the time required to perform nucleic acid processing procedures before performing nucleic acid analysis and detection, improve execution efficiency, and can also effectively utilize the internal space of the integrated nucleic acid processing equipment 1 to achieve the purpose of minimizing the volume.

It should be noted that the above are only preferred embodiments proposed to illustrate this case. This case is not limited to the embodiments described. The scope of this case is determined by the scope of the attached patent application. Moreover, this case may be modified in various ways by those who are familiar with this technology, but it will not deviate from the intended protection within the scope of the attached patent application.

1: Integrated nucleic acid processing equipment 10: Shell 101:Linear module 1011:Door bracket 1012:Cam 1013:Spring 1014: Spring bracket 1015: Linear guide 1016:Skateboard 1017:Slider 102: Driving side slide rail 103: Driven side slide rail 104: Installation bracket 105: Guide plate 1051:Trench 11:Door 111:Door frame 112:Door panel 113: Handle 12: Operation interface 20: First operating area 21a: First air inlet 21b: First air outlet 22: Inspection tube bearing plate 220: Inspection tube 2201: Row type inspection tube rack 2202: Disk type sampling tube rack 221: First sampling tube placement area 222: Second collection tube placement area 223: Hollow part 224: Nucleic acid detection tray 225: Reagent tube rack 2250: Reagent tube 226: Cooling module 227: Interchangeable transfer plate 23: Pipette carrying plate 230: Pipette 2301a: 96-well pipette rack 2301b: 24-well pipette rack 231: Well plate 24a, 24b: Extraction reagent well plate carrier plate 241: Extraction reagent well plate 242: Heating module 25a: Bottom scanner 26: Collection of operating function modules 260: Base 261: Pipette gun module 2611: Pipette gun set 2612: Pipette gun 2613: Pipette gun fixing plate 2614:Chassis 262:Screw switch cover module 2621:Cylinder 2622:Thread 2624:Chassis 263:Clamp switch cover module 2631:Clamp 264:Visual recognition module 2641:Bracket 27:Baffle 30: Second operating area 31, 32: Extraction area 31a: Second air inlet 31b: Second air outlet 311, 321: Magnetic rod holder 3111, 3211: Magnetic rod 312, 322: Magnetic rod sleeve connector holder 3121, 3221: Magnetic rod sleeve connector 40: Mechanical and electrical configuration area 50: Next door to the area 51a, 51b: Door piece A: Round frame X, Y, Z: X axis, Y axis, Z axis

Figure 1 shows a schematic diagram of the integrated nucleic acid processing equipment in this embodiment. Figure 2A shows a schematic diagram of the door and its mounting components according to the embodiment of the present invention. Figure 2B shows an enlarged view of the circle A in Figure 2A. Figure 3A shows a perspective view of the integrated nucleic acid processing equipment according to this embodiment. Figure 3B shows another perspective view of the integrated nucleic acid processing equipment of this embodiment. Figure 4 shows a schematic diagram of the collection of load plates in the first operating area of the embodiment of the present invention. Figure 5A shows a schematic diagram of the inspection tube bearing plate and its configuration in the embodiment of this case. Figure 5B shows another schematic diagram of the sampling tube carrying plate and the configuration thereon according to the embodiment of this case. Figure 6 shows a schematic diagram of the pipette carrying plate and its configuration in this embodiment. Figures 7A-7B show a schematic diagram of the extraction reagent well plate carrier plate and its configuration in the second embodiment of this case. Figure 8 shows a perspective view of the second operating area of the embodiment of the present invention. Figure 9A shows a perspective view of the operation function module assembly according to the embodiment of the present invention. Figure 9B shows another perspective view of the operating function module assembly according to the embodiment of the present invention. Figure 10 shows an exploded schematic diagram of the operation function module set in this embodiment of the present invention.

1: Integrated nucleic acid processing equipment

10: Shell

12: Operation interface

20: First operating area

21a: First air inlet

26: Collection of operating function modules

27:Baffle

30: Second operating area

31a: Second air inlet

40: Mechanical and electrical configuration area

50: next door

X, Y, Z: X axis, Y axis, Z axis

Claims (19)

An integrated nucleic acid processing device, including: A first operating area, including: A collection and inspection tube carrying plate for placing a plurality of collection and inspection tubes; A pipette carrying plate for placing at least one pipette rack, each pipette rack including a plurality of pipettes; Two extraction reagent well disk carrier plates, each extraction reagent well disk carrier plate carries a plurality of extraction reagent well disks, and a plurality of magnetic rod sets are preset in each extraction reagent well disk; A barcode scanner used to scan a plurality of barcodes provided on the plurality of sampling tubes; A pipette module used to combine the plurality of pipettes to move a plurality of samples from the plurality of sampling tubes to at least one of the plurality of extraction reagent well plates; a switch cover module for opening and closing a plurality of covers of the plurality of sampling tubes; and A visual recognition module includes a camera for capturing internal images of the first operating area, The sampling tube carrying plate, the pipette carrying plate, and the two extraction reagent well plate carrying plates are respectively set up on a track to move in the X-axis direction. The pipette gun module and the visual recognition module move in the Y-axis direction and the Z-axis direction; A second operating area is divided into two extraction areas up and down, and each extraction area includes: a magnetic rod holder for mounting a plurality of magnetic rods; and A magnetic rod sleeve connector rack used to set up a plurality of magnetic rod sleeve connectors to connect the magnetic rod sleeves pre-placed in the extraction reagent well plates; and A partition wall is used to separate the first operating area and the second operating area, and includes two door pieces corresponding to the two extraction areas, The two extraction reagent well plate carrier plates are arranged up and down corresponding to the two door pieces, and can be moved from the first operating area to the second operating area when the two door pieces are opened, and can be moved to the isolated space when the two door pieces are closed. A plurality of nucleic acid extraction operations utilizing the plurality of magnetic rods, the plurality of magnetic rod sleeve connectors, and the plurality of magnetic rod sleeves are performed in the second operation area. The integrated nucleic acid processing equipment as described in claim 1, wherein the extraction reagent well plate carrier plate and the collection tube carrier plate located below are located on a first plane, and the two can be selectively synchronized through mechanical combination. Move. The integrated nucleic acid processing equipment of claim 2, wherein the pipette carrier plate is located on a second plane, and the second plane is higher than the first plane, and the extraction reagent well plate carrier plate is located above It is located on a third plane, and the third plane is higher than the second plane. The integrated nucleic acid processing equipment as described in claim 1 further includes a casing so that an independent space is formed inside the integrated nucleic acid processing equipment, and the casing has a door for opening. The integrated nucleic acid processing equipment as described in claim 4, wherein the door, the first operating area, and the second operating area are sequentially arranged along the X-axis direction. The integrated nucleic acid processing equipment as claimed in claim 1, wherein the first operating area and the second operating area have independent air circulation systems respectively, and each air circulation system has an air flow from a lower place to a higher place. direction of flow. The integrated nucleic acid processing equipment as described in claim 1 further includes a high-efficiency filter (HEPA) to filter the air entering and exiting the first operating area and the second operating area respectively. Integrated nucleic acid processing equipment as described in claim 1, wherein the collection tube carrier plate has a plurality of hollow parts corresponding to the plurality of collection tubes, and the barcode scanner includes a bottom scanner to scan the The plurality of barcodes on the bottoms of the plurality of sampling tubes. The integrated nucleic acid processing equipment as claimed in claim 1, wherein the barcode scanner includes a side scanner to scan the plurality of barcodes provided on the sides of the plurality of collection tubes. The integrated nucleic acid processing equipment as described in claim 1, wherein the collection tube carrying plate has a first collection tube placement area and a second collection tube placement area to respectively carry different forms of collection tubes. The integrated nucleic acid processing equipment as described in claim 1, wherein a nucleic acid detection tray is further placed on the collection tube carrier plate to accommodate the nucleic acids obtained after the plurality of nucleic acid extraction operations. As for the integrated nucleic acid processing equipment described in claim 1, a reagent tube rack is further placed on the test tube carrier plate to place a plurality of reagent tubes, and a cold storage module is provided for the reagent tube rack. The integrated nucleic acid processing equipment of claim 1, wherein the plurality of pipettes are placed back into the at least one pipette rack after use. The integrated nucleic acid processing equipment as described in claim 1, wherein a well plate is further placed on the pipette carrier plate to serve as a nucleic acid detection plate or an extraction nucleic acid sample retention plate. The integrated nucleic acid processing equipment of claim 1, wherein each extraction reagent well plate carrier plate includes a heating module to provide temperature changes required for the plurality of nucleic acid extraction operations. The integrated nucleic acid processing equipment as claimed in claim 1, wherein the switch cover module includes a screw switch cover module and a claw switch cover module. The integrated nucleic acid processing equipment as described in claim 1 further includes a plurality of chassis, which are respectively disposed under the pipette module and the switch cover module. The integrated nucleic acid processing equipment as described in claim 1 further includes ultraviolet (UV) lamps, which are respectively installed in the first operating area and the second operating area for cleaning and sterilization. The integrated nucleic acid processing equipment as described in claim 1 further includes a controller and at least one motor to respectively control and drive the collection tube carrier plate, the pipette carrier plate, and the two extraction reagent well plate carrier plates , the pipetting gun module, the barcode scanner, the switch cover module, the visual recognition module, the magnetic rod holder, the magnetic rod sleeve connector holder, and the two door pieces.

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